抗α_1-肾上腺素受体抗体介导大鼠心室重塑的免疫机制  

Immune mechanism of cardiac remodeling induced by antibodies against to the α_1-adrenergic receptor

作　　者：周子华[1] 廖玉华[1] 李留东[1] 王彬[1] 魏芬[1] 王敏[1] 魏宇淼[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管病研究所心血管病免疫实验室,武汉430022

出　　处：《中华医学杂志》2005年第9期625-629,共5页National Medical Journal of China

基　　金：国家973高技术计划发展基金资助项目(G2000056900)

摘　　要：目的观察抗α1肾上腺素受体自身抗体对大鼠心室重塑的影响并探索其可能机制。方法用α1肾上腺素受体胞外第二肽段合成肽免疫Wistar大鼠作为模型,设自发性高血压大鼠及正常Wistar大鼠为对照;用尾套法监测收缩压及心率,用酶联免疫吸附试验(ELISA)法检测抗α1肾上腺素受体抗体滴度,用光镜和电镜观察并计算心脏病理变化;用逆转录多聚合酶链式反应(RT PCR)、免疫印迹及免疫组织化学的方法检测左心室肌组织的c jun和/或c fos、α1肾上腺素受体的表达。结果在免疫后2周抗α1肾上腺素受体抗体滴度开始升高,并在整个实验过程中维持在较高水平;在实验过程中,免疫组血压心率与对照组差异无统计学意义,但均显著低于自发性高血压大鼠组;免疫组心脏体重比、左心室心肌细胞截面积、心肌胶原体积比例和心肌血管周围胶原面积与管腔面积比例分别为3.32mg/g±0.25mg/g、231μm2±11μm2、5.40%±0.66%和1.89±0.62,均显著高于正常对照组(分别为3.06mg/g±0.25mg/g、197μm2±19μm2、3.22%±0.15%和0.86±0.17),但低于自发性高血压大鼠组;电镜结果显示心肌细胞肥大、线粒体增多,心肌间质胶原纤维增多,说明免疫组发生心室重塑;在免疫组中,α1A、B肾上腺素受体及c fos的表达与正常对照差异无统计学意义,但α1D肾上腺素受体表?Objective To study the effects of autoantibodies against α1-adrenergic receptor on the cardiac remodeling and relevant mechanism. Methods Four-week-old male Wistar rats were immunized with synthesized second extracellular loop of α1-adrenergic receptor and raised for one year, with spontaneously hyperetensive rats (SHRs) and no-immunized Wistar rats of the same age as controls. Every one or two months blood was collected from the caudal vein to detect the level of serum antibodies to α1-adrenergic receptor by ELISA and the systolic blood pressure (SBP) and heart rate were measured. One year after the rats were killed and their hearts were taken out. The heart weight/body weight ratio,cardiac muscle cell cross-sectional area (CSA) ,interstitial collagen volume fraction (CVF) and the ratio of perivascular collagen area to vessel luminal area (PVCA) were calculated, the expression of α1-adrenergic receptor, c-fos and c-Jun in heart were measured by RT-PCR, Western blotting and immunohistochemistry. Results During the experiment the blood pressure of the SHRs were significantly higher than those of the immunization group and normal control group (both P<0.01) without significant difference between the 2 latter groups. The heart weight/body weight ratio, CSA, CVF and PVCA of the immobilization group were 3.32 mg/g±0.25 mg/g, 231 μm2±11 μm2, 5.40%±0.66% and 1.89±0.62 respectively, all significantly higher than those of the normal control group (3.06 mg/g±0.25 mg/g, 197 μm2±19 μm2, 3.22%±0.15% and 0.86±0.17 respectively), but still significantly lower than those of the SHR group. Since the second week after immunization, the titre of antibody against of the immunization group began increase, peaked in the second and third months, and then decreased slowly, and remained at a high level by the end of experiment. The titre of antibody was not correlated with blood pressure. Hypertrophy of cardiac muscle cells and increase of sedimentation of collagen in stroma were seen in the hearts of the immunization gro

关 键 词：Α1-肾上腺素受体 心室重塑 免疫组 正常 大鼠 表达 对照组 实验过程 高水平 体积比 

分 类 号：R541[医药卫生—心血管疾病]